Dietary flavonoids show beneficial effects in the prevention of chronic diseases. However, flavonoid bioavailability is poor, probably due to their interaction with serum albumins. In the current work, the binding interactions of eight related flavonoids, sharing a similar core structure, with bovine serum albumin (BSA) were investigated by fluorescence spectroscopy. The binding affinities of the flavonoids with BSA were in the order hesperetin (KA=5.59 × 105) > quercetin (4.94 × 105) > naringenin (3.04 × 105) > isoquercitrin (4.66 × 104) > icariin (3.60 × 104) > rutin (1.65 × 104) > hesperidin (2.50 × 103) > naringin (8.70 × 102). The associations of specific structural components of the flavonoids with their binding properties to BSA were also explored and hydrophobicity, functional group substituents, steric hindrance effects and the spatial arrangements of substituents seem to be the key factors for the affinities of flavonoids towards BSA. The results from the current work contribute to a better understanding of the transport of flavonoids in plasma and helping predict their physiological functions based on their intrinsic structures.